Therapeutic innovation & regulatory science最新文献

{"title":"Descriptions of Abnormal Kidney Function in Contraindications: A Cross-Sectional Analysis of Japanese Prescription Drug Labeling Under the New Format.","authors":"Masahiro Kobayashi, Momo Watanabe, Mika Maeda, Tatsuya Okuwaki, Katsuya Otori","doi":"10.1007/s43441-025-00868-x","DOIUrl":"https://doi.org/10.1007/s43441-025-00868-x","url":null,"abstract":"<p><strong>Background: </strong>In Japan, prescription drug labeling has transitioned to a new structured format aimed at improving clarity and consistency, with full implementation in March 2024. Abnormal kidney function, a critical determinant of drug safety, necessitates clear and consistent contraindication labeling. However, current labeling practices have not been comprehensively evaluated.</p><p><strong>Objective: </strong>To systematically assess how kidney-related contraindications are described in Japanese package inserts under the new labeling format.</p><p><strong>Methods: </strong>We reviewed all electronically available prescription drug package inserts as of October 1, 2024. Using 20 kidney-related keywords, we extracted and analyzed statements in Sect. 2 (\"Contraindications\"), categorizing them into four domains: type of impairment, severity, disease progression, and quantitative criteria. Additionally, a network diagram of co-occurring terms was developed to illustrate the consistency and diversity of terminology.</p><p><strong>Results: </strong>A total of 233 kidney-related contraindication statements were identified across 182 pharmaceutical ingredients. Type of impairment was mentioned in 81.5%, severity in 54.9%, and quantitative criteria in 38.2%. However, the terminology and threshold values used were inconsistent. Terms such as \"severe abnormal kidney function\" were used without standardized definitions, and quantitative parameters (e.g., creatinine clearance, estimated glomerular filtration rate) varied across products.</p><p><strong>Conclusion: </strong>Despite regulatory efforts to enhance labeling structure, kidney-related contraindication descriptions in Japan remain variable and lack standardization. These inconsistencies may hinder safe prescribing practices and the integration of labeling into clinical decision support systems. Adoption of internationally harmonized terminology, such as KDIGO staging, and clearer regulatory guidance may improve the clinical utility of drug labeling.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Screen Formats: Towards Context-Aware, Patient-Centric ePRO Design in Clinical Trials.","authors":"Schawanya Kaewpitoon Rattanapitoon, Nav La, Patpicha Arunsan, Nathakapch Kaewpitoon Rattanapitoon","doi":"10.1007/s43441-025-00869-w","DOIUrl":"https://doi.org/10.1007/s43441-025-00869-w","url":null,"abstract":"<p><p>Lord-Bessen et al. demonstrated that both single-item-per-screen and multiple-items-per-screen ePRO formats are acceptable, with minimal differences in usability and completion time. While format preference may be individual-specific, broader considerations-including patient cognitive load, device type, language complexity, and trial phase-are crucial for context-aware ePRO design. Future research should explore adaptive systems that dynamically adjust format in real time, subgroup analyses for older adults and low digital literacy participants, and language-specific validation. Moving beyond fixed formats toward adaptive, patient-tailored delivery can better align with regulatory priorities for patient-focused drug development, enhancing both participant experience and data integrity.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning in Tuberculosis Research: A Global Bibliometric Analysis of Diagnostic, Prognostic, and Drug Discovery Trends.","authors":"Siddig Ibrahim Abdelwahab, Manal Mohamed Elhassan Taha, Hazem Mathkour, Edrous Alamer, Saleh Mohammad Abdullah, Saeed Alshahrani, Abdullah Mohammed Farasani, Ahmed S Alamer, Jobran M Moshi, Khaled A Sahli, Mohammed Jeraiby, Nizar A Khamjan, Abdulwahab Binjomah","doi":"10.1007/s43441-025-00866-z","DOIUrl":"https://doi.org/10.1007/s43441-025-00866-z","url":null,"abstract":"<p><strong>Background and objectives: </strong>Tuberculosis (TB) remains a major global health challenge, driving the need for innovative approaches in diagnosis and drug development. The integration of artificial intelligence (AI), particularly machine learning (ML), has enabled significant advancements in areas such as drug resistance prediction, radiomics, prognostic modeling, and computational drug discovery. This study presents a comprehensive bibliometric analysis of global research on machine learning and tuberculosis (MLTB), highlighting trends relevant to therapeutic innovation and regulatory science.</p><p><strong>Methods: </strong>A structured search of the Scopus database was conducted for English-language, data-driven publications on MLTB through May 1, 2024. Bibliometric indicators were analyzed using Biblioshiny and VOSviewer, focusing on publication trends, citation metrics, collaboration networks, and thematic clustering.</p><p><strong>Results: </strong>The MLTB research field has grown rapidly, with an average annual growth rate of 22.12% between 2000 and 2024. Publications averaged 21.64 citations, and 40.11% involved international collaboration. Twelve major clusters were identified, including deep learning, drug discovery, bioinformatics, docking, random forest, and latent TB infection-highlighting the field's expanding scope in drug development and diagnostic applications.</p><p><strong>Conclusion: </strong>MLTB research is evolving rapidly, driven by interdisciplinary collaboration and AI innovation. These findings offer insights for guiding future AI-enabled TB therapeutic strategies and aligning research efforts with regulatory and translational priorities.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient Safety in Healthcare: A Proposal for Ensuring the Use of Regulation-Compliant Safety Devices.","authors":"Tuncay Bayrak","doi":"10.1007/s43441-025-00863-2","DOIUrl":"https://doi.org/10.1007/s43441-025-00863-2","url":null,"abstract":"<p><p>Medical devices used in health care should fulfill the requirements of the technical regulations to protect patient health. Difficulties in enforcing stricter rules in the new medical device regulations may negatively affect the continuity of care. This study examines the status of manufacturers' compliance with medical device regulations, based on predefined criteria, and proposes a collaborative action plan and an approach to verify regulatory compliance. We conducted a nationwide survey comprising questions grouped by criteria to understand the status of the manufacturers in terms of compliance with the Medical Device Regulation. Four hundred sixty-seven manufacturers participated in the survey. We achieved a Cronbach's alpha of 0.77, which indicates that the survey is statistically reliable. We applied the independent samples t-test to the responses to determine significant features per question and employed factor analysis to investigate the relationships of the questions. The results of independent samples t-tests showed statistically significant differences across groups in replies to several survey items (p < 0.05), indicating that participants' opinions varied based on their demographic characteristics. We applied Exploratory Factor Analysis to introduce the relationships between the questions. The analysis revealed that manufacturers continue to face substantial challenges in acquiring sufficient knowledge and operational capability to meet MDR requirements. In light of these findings, we focused on the person responsible for regulatory compliance, who plays a central role in maintaining regulatory compliance within manufacturing organizations. We proposed an action plan at the macro level to introduce more effective action plans in cooperation with other stakeholders, including healthcare providers, and a verification approach for regulatory compliance to enhance the Person Responsible for Regulatory Compliance's competence. Manufacturers should implement effective postmarketing clinical follow-up plans involving device-oriented parameters for monitoring in the healthcare system, especially in collaboration with health professionals.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measuring Patient Participation Burden in Clinical Outcome Assessments for Clinical Trials.","authors":"Abigail Dirks, Hana Do, Chelsea Gallagher, Arnab Roy, Tricia Siddharth, Emily Szabo, Kenneth Getz","doi":"10.1007/s43441-025-00832-9","DOIUrl":"https://doi.org/10.1007/s43441-025-00832-9","url":null,"abstract":"<p><strong>Background: </strong>Bristol Myers Squibb (BMS), in collaboration with ZS and Tufts CSDD, recently conducted a detailed evaluation of participation burden associated with clinical outcome assessments, including patient reported outcomes.</p><p><strong>Methods: </strong>A mixed-methods approach was used including an online global survey followed by in-depth interviews with patients and investigative sites to understand underlying causes of participation burden.</p><p><strong>Results: </strong>258 patients completed the online survey, 12 interviews were conducted among patients, and 12 interviews were conducted among investigative site personnel. The results show significant differences in patient perceptions of participation burden depending on the modalities and types of clinical outcome assessments administered in clinical trials. Specific modalities associated with elevated burden included those longer than 30 min and those completed several times per month. Perceived burden of clinical outcome assessments varied significantly by patient age and ethnicity. Investigative sites also reported the burden associated with administering electronic clinical outcome assessments - most notably the technical challenges and additional patient assistance required during initial setup, first patient visit, and technology management across different sponsors.</p><p><strong>Conclusion: </strong>The results of this study raise clinical team and protocol author awareness of the patient participation burden associated with distinct types and modalities of clinical outcome assessments and informs decisions to selectively reduce this burden. The results of this study build on the Tufts CSDD-ZS Patient Burden Algorithm.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implementation of Established Conditions and Use of Quality by Design Principles during Drug Development: Status in the US, EU, and Japan. Data from a Survey Conducted by the Japan Pharmaceutical Manufacturers Association (JPMA).","authors":"Yoshio Nakayama, Sonoko Yamauchi, Kozue Shimizume, Akinobu Nakanishi, Maki Masuyama, Yasuyo Ozaki, Koji Nakamura, Makoto Fujikawa, Masatsugu Kobayashi, Yuji Kashitani","doi":"10.1007/s43441-025-00856-1","DOIUrl":"https://doi.org/10.1007/s43441-025-00856-1","url":null,"abstract":"<p><p>The JPMA conducted a survey among its member companies regarding the use of Established Conditions (ECs) under ICH Q12. ECs can be set by companies that develop new drugs using the Quality by Design (QbD) approach defined in ICH Q8 and have an effective Pharmaceutical Quality System (PQS) as per ICH Q10. The survey revealed that while the use of QbD has increased, surpassing 70% in Japan since 2021, the adoption of ECs in New Drug Application (NDA) submissions remains low due to a lack of legal framework and internal understanding. More companies were using ECs in post-approval changes (PACs) compared to NDA submissions. The survey also found that companies prefer the existing systems in each region when determining the change category during change initiation. While Europe and the US believe that risk assessment of changes and ECs are consistent with an effective PQS, Japan perceives a mismatch between change assessment and predetermined change categories at the time of approval. This results in Japan willing to have an option applying the risk assessment at change control to reporting category evaluation. Considering these circumstances, it is anticipated that the use of ECs will gradually expand, primarily in PACs. The discrepancies in change procedures among countries may hinder a stable supply, so Japan should consider introducing change guidelines similar to those in Europe and the US to facilitate a hybrid approach to approvals that can accommodate the expanded use of ECs.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Company Sponsored Platform Trials: Recommendations and Lessons Learned from Cross-Industry Interviews.","authors":"Yujun Wu, Chengxing Cindy Lu, Mehreteab Aregay, Kristine Broglio, Yingwen Dong, Cooner Freda, Wei He, Bo Huang, Nicole Li, Haijun Ma, Peter Mesenbrink, Casey Xu, Lina Yin","doi":"10.1007/s43441-025-00792-0","DOIUrl":"10.1007/s43441-025-00792-0","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144875378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Real-World Disproportionality Analysis of FDA Adverse Event Reporting System Events for Tazemetostat.","authors":"Qiong Liu, Miaoqing Luo, Mengge Gao, Bo Yang, Xiaofang Liu, Guojun Liang","doi":"10.1007/s43441-025-00845-4","DOIUrl":"10.1007/s43441-025-00845-4","url":null,"abstract":"<p><strong>Background: </strong>Tazemetostat, an EZH2 inhibitor approved for select sarcomas and lymphomas, has limited post-marketing safety data despite growing clinical use. This study aimed to evaluate the real-world safety profile of tazemetostat using data from the FDA Adverse Event Reporting System (FAERS) between Q1 2020 and Q4 2024.</p><p><strong>Methods: </strong>Reports listing tazemetostat as the primary suspect drug were extracted, deduplicated, and analyzed using four disproportionality methods. Preferred Terms (PTs) were standardized via MedDRA 26.1 and mapped to System Organ Classes (SOCs). Subgroup analyses and time-to-onset assessments were performed across age, sex, and reporter types.</p><p><strong>Results: </strong>A total of 1,179 adverse event reports associated with tazemetostat were retrieved from FAERS. Disproportionality analysis revealed significant signals across gastrointestinal, hematologic, and general systemic domains. Fatigue, nausea, decreased appetite, and anemia were the most commonly reported events. Significantly, taste disorder and somnolence were identified as new signals that were not present in FDA labeling. Most events occurred within the first 60 days of treatment, with similar onset patterns across demographic subgroups.</p><p><strong>Conclusion: </strong>This FAERS-based analysis confirmed known toxicities and identified novel signals associated with tazemetostat in routine clinical use. These findings underscore the importance of continued pharmacovigilance to detect emerging adverse events and inform real-world monitoring strategies.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Master Protocols: A Promising Approach to Accelerate Drug Development in Rare Kidney Diseases.","authors":"Julie Lin, Jai Radhakrishnan","doi":"10.1007/s43441-025-00857-0","DOIUrl":"10.1007/s43441-025-00857-0","url":null,"abstract":"<p><p>Kidney diseases have been a highly challenging area for new drug development because of traditional requirements for reaching doubling of serum creatinine, dialysis, or transplantation endpoints for regulatory approval, which translates into clinical trials needing several years of follow up and large numbers of study participants to achieve adequate power. In recent years, however, progress in surrogate endpoints (specifically proteinuria reduction and slowing of estimated glomerular filtration rate decline in rare glomerular diseases) has resulted in greatly increased interest by biotechnology and pharmaceutical sponsors in investing in these indications.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Regulatory Perspective on a UK Federated Data Network for Medicines and Medical Devices: Lessons from a 'Study-A-Thon'.","authors":"Helen P Booth, John Connelly, Daniel Dedman, Katherine Donegan, Alison Cave","doi":"10.1007/s43441-025-00854-3","DOIUrl":"10.1007/s43441-025-00854-3","url":null,"abstract":"<p><p>Internationally, medical regulators are seeking to make better use of real-world data (RWD) to support their decision making. While the UK National Health Service collects population-wide cradle-to-grave data, challenges remain around siloing, interoperability and access to data across different care settings. In 2023, a `Study-A-Thon' was held to explore how mobilisation of a UK distributed data network might be used to generate real-world evidence (RWE) for regulatory purposes by increasing availability of RWD in a timely manner. Two research questions focusing on high-priority data gaps (medical devices and secondary care prescribing) were selected as case studies to support this work. This paper summarises details of the Study-A-Thon and discusses key learnings for the UK's Medicines and Healthcare products Regulatory Agency (MHRA), UK stakeholders and international partners to reflect on when developing and implementing RWD strategies. Shortcomings of the data are discussed, such as a lack of follow-up for patients across care settings and the need to develop common data models to capture relevant information on medical product utilisation. The importance of local data and clinical expertise for success is highlighted, from encouraging better data collection at point of care through to appropriate interpretation of results. Successful delivery of results for both studies supports the view that, with further development, a UK federated data model could enhance national regulatory decision-making across the product lifecycle.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}